Genetics of Adiposity and Glucose Homeostasis

肥胖和血糖稳态的遗传学

基本信息

批准号：
7540880
负责人：
JILL M NORRIS
金额：
$ 13.95万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2011-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The IRAS Family Study, initially funded as six linked R01s in 1999, is a multicenter project designed to study the genetic epidemiology of adiposity and glucose homeostasis. The recruitment and phenotyping components have been completed in the three clinical centers. All families were of African-American or Hispanic descent. A total of 132 extended families (1861 subjects) have been studied for measurement of adiposity by abdominal CT scan and glucose homeostasis using the insulin-modified frequently sampledintravenous glucose tolerance test (FSIGT). These investigations have identified substantial genetic contribution to measures of adiposity (visceral and sub-cutaneous fat, BMI and waist circumference) and glucose homeostasis (insulin sensitivity, glucose effectiveness, acute insulin response to glucose, disposition index, fasting glucose and fasting insulin). A 10 cM genome scan of the IRAS Family Study DNA has been completed. Linkage analyses have identified several genomic regions related to adiposity and glucose homeostasis. Several of these signals have been followed-up with fine mapping. This renewal application, entitled Genetics of Adiposity and Glucose Homeostasis, targets the further exploration of genomic regions and positional cloning of genes contributing to variation in adiposity and glucose homeostasis. Positional candidate genes will be identified. We will also re-contact the original cohort to repeat some of the primary phenotypes for measures of change (abdominal CT scan and fasting insulin) and add several important new phenotypes to add depth to our assessment of adiposity and glucose homeostasis (total body fat by DXA and adipocytokines, including adiponectin and soluble TNF-alpha receptors 1 and 2). A panel of nutritional, dietary, and eating behaviors will be assessed in which to study the genetic effects. Using the existing genome scan data and variance-components-based linkage analysis methods, regions of the genome will be detected that contribute to variation in these new phenotypes and in the change phenotypes. The proposed study is unique in its performance of gone discovery for adiposity and glucose homeostasis in a multi-ethnic (non-majority) sample while simultaneously examining the genetic and environmental correlations among these and other metabolic phenotypes.

描述（由申请人提供）：IRAS 家族研究最初于 1999 年以六联 R01 的形式资助，是一个多中心项目，旨在研究肥胖和葡萄糖稳态的遗传流行病学。三个临床中心已完成招募和表型分析部分。所有家庭都是非裔美国人或西班牙裔美国人后裔。总共对 132 个大家庭（1861 名受试者）进行了研究，通过腹部 CT 扫描测量肥胖情况，并使用胰岛素改良频繁采样静脉葡萄糖耐量试验 (FSIGT) 测量血糖稳态。这些研究已确定遗传因素对肥胖（内脏和皮下脂肪、体重指数和腰围）和葡萄糖稳态（胰岛素敏感性、葡萄糖有效性、胰岛素对葡萄糖的急性反应、处置指数、空腹血糖和空腹胰岛素）的测量有重大贡献。 IRAS 家族研究 DNA 的 10 cM 基因组扫描已经完成。连锁分析已经确定了与肥胖和葡萄糖稳态相关的几个基因组区域。其中一些信号已通过精细映射进行了跟踪。这项更新申请题为《肥胖和葡萄糖稳态遗传学》，旨在进一步探索基因组区域和对导致肥胖和葡萄糖稳态变化的基因进行位置克隆。将鉴定位置候选基因。我们还将重新联系最初的队列，重复一些主要表型以测量变化（腹部 CT 扫描和空腹胰岛素），并添加几个重要的新表型，以增加我们对肥胖和葡萄糖稳态评估的深度（全身脂肪通过DXA 和脂肪细胞因子，包括脂联素和可溶性 TNF-α 受体 1 和 2)。将评估一组营养、饮食和饮食行为，以研究遗传效应。使用现有的基因组扫描数据和基于方差成分的连锁分析方法，将检测到导致这些新表型和变化表型变异的基因组区域。这项研究的独特之处在于它在多种族（非多数）样本中发现了肥胖和葡萄糖稳态，同时检查了这些和其他代谢表型之间的遗传和环境相关性。